Vasić, Marko

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orcid::0000-0003-2115-5901
  • Vasić, Marko (3)
  • Vasić, Marko S. (1)

Author's Bibliography

Description of a new potential aggregation factor from the Streptococcus thermophilus genome

Tsibulskaya, Darya; Blagojević, Veljko; Terzić-Vidojević, Amarela; Lukić, Ivana; Vasić, Marko; Dragačević, Luka; Kojić, Milan

(Serbian Society for Microbiology, 2024)

TY  - CONF
AU  - Tsibulskaya, Darya
AU  - Blagojević, Veljko
AU  - Terzić-Vidojević, Amarela
AU  - Lukić, Ivana
AU  - Vasić, Marko
AU  - Dragačević, Luka
AU  - Kojić, Milan
PY  - 2024
UR  - http://intor.torlakinstitut.com/handle/123456789/875
AB  - Autoaggregation, the ability to self-aggregate, is widespread among both Gram-positive and Gram-negative bacteria. The functional role of aggregation is not fully understood, but it is believed to be involved in the adaptation of bacteria to environmental conditions (PMID: 31294207). One interesting class of compounds responsible for the aggregation of lactic acid bacteria is aggregation factors—surface high-molecular-weight proteins rich in threonine and lysine (PMID: 30027759). Recently, our research group discovered a new strain of Streptococcus thermophilus in the mountainous regions of Serbia, exhibiting an aggregation phenotype. Aggregation phenotype was confirmed visually and using microscopy. Complete genome of Agg+ strain was sequenced using NGS and a gene encoding a potential aggregation factor, which was named aggS was identified. The predicted threonine (12.5%) and lysine (10.5%) rich protein contains 2367 amino acids, with an average molecular weight of 255986.63 Da. AggS also contains two cysteine residues, whereas previously well-described aggregation factors of this type did not contain any cysteine residues. The predicted protein includes an N-terminal YSIRK-like signal sequence and an LPXTG cell wall anchor domain. It has 6 Mucin binding domain repeats alternating with 6 Mub B2-like domain repeats. Additionally, we found a region resembling an ice-binding domain. Given that these bacteria endure prolonged periods of low temperatures, it can be speculated that this surface membrane protein also helps the bacteria withstand freezing. The fact that the alignment using BLASTp revealed AggS to be most closely related to an uncharacterised protein from the genome of Lactococcus garvieae, along with the discovery of a transposase gene sequence upstream of the gene, suggests that the aggregation factor was likely acquired through horizontal gene transfer. We plan to clone it into a shuttle vector and investigate the aggregation phenotype using a heterologous expression system in Lactococcus lactis, as well as explore its other functions.
PB  - Serbian Society for Microbiology
C3  - XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april
T1  - Description of a new potential aggregation factor from the Streptococcus thermophilus genome
EP  - 110
SP  - 110
UR  - https://hdl.handle.net/21.15107/rcub_intor_875
ER  - 
@conference{
author = "Tsibulskaya, Darya and Blagojević, Veljko and Terzić-Vidojević, Amarela and Lukić, Ivana and Vasić, Marko and Dragačević, Luka and Kojić, Milan",
year = "2024",
abstract = "Autoaggregation, the ability to self-aggregate, is widespread among both Gram-positive and Gram-negative bacteria. The functional role of aggregation is not fully understood, but it is believed to be involved in the adaptation of bacteria to environmental conditions (PMID: 31294207). One interesting class of compounds responsible for the aggregation of lactic acid bacteria is aggregation factors—surface high-molecular-weight proteins rich in threonine and lysine (PMID: 30027759). Recently, our research group discovered a new strain of Streptococcus thermophilus in the mountainous regions of Serbia, exhibiting an aggregation phenotype. Aggregation phenotype was confirmed visually and using microscopy. Complete genome of Agg+ strain was sequenced using NGS and a gene encoding a potential aggregation factor, which was named aggS was identified. The predicted threonine (12.5%) and lysine (10.5%) rich protein contains 2367 amino acids, with an average molecular weight of 255986.63 Da. AggS also contains two cysteine residues, whereas previously well-described aggregation factors of this type did not contain any cysteine residues. The predicted protein includes an N-terminal YSIRK-like signal sequence and an LPXTG cell wall anchor domain. It has 6 Mucin binding domain repeats alternating with 6 Mub B2-like domain repeats. Additionally, we found a region resembling an ice-binding domain. Given that these bacteria endure prolonged periods of low temperatures, it can be speculated that this surface membrane protein also helps the bacteria withstand freezing. The fact that the alignment using BLASTp revealed AggS to be most closely related to an uncharacterised protein from the genome of Lactococcus garvieae, along with the discovery of a transposase gene sequence upstream of the gene, suggests that the aggregation factor was likely acquired through horizontal gene transfer. We plan to clone it into a shuttle vector and investigate the aggregation phenotype using a heterologous expression system in Lactococcus lactis, as well as explore its other functions.",
publisher = "Serbian Society for Microbiology",
journal = "XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april",
title = "Description of a new potential aggregation factor from the Streptococcus thermophilus genome",
pages = "110-110",
url = "https://hdl.handle.net/21.15107/rcub_intor_875"
}
Tsibulskaya, D., Blagojević, V., Terzić-Vidojević, A., Lukić, I., Vasić, M., Dragačević, L.,& Kojić, M.. (2024). Description of a new potential aggregation factor from the Streptococcus thermophilus genome. in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april
Serbian Society for Microbiology., 110-110.
https://hdl.handle.net/21.15107/rcub_intor_875
Tsibulskaya D, Blagojević V, Terzić-Vidojević A, Lukić I, Vasić M, Dragačević L, Kojić M. Description of a new potential aggregation factor from the Streptococcus thermophilus genome. in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april. 2024;:110-110.
https://hdl.handle.net/21.15107/rcub_intor_875 .
Tsibulskaya, Darya, Blagojević, Veljko, Terzić-Vidojević, Amarela, Lukić, Ivana, Vasić, Marko, Dragačević, Luka, Kojić, Milan, "Description of a new potential aggregation factor from the Streptococcus thermophilus genome" in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april (2024):110-110,
https://hdl.handle.net/21.15107/rcub_intor_875 .

Determination of muscle fiber types expressing ANKRD2

Novković, Mirjana; Vasić, Marko; Jasnić, Jovana; Milošević, Emilija; Milovanović, Mina; Savić, Slobodan; Kojić, Snežana

(Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade, 2023)

TY  - CONF
AU  - Novković, Mirjana
AU  - Vasić, Marko
AU  - Jasnić, Jovana
AU  - Milošević, Emilija
AU  - Milovanović, Mina
AU  - Savić, Slobodan
AU  - Kojić, Snežana
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2114
UR  - http://intor.torlakinstitut.com/handle/123456789/806
AB  - Introduction: Ankyrin Repeat Domain 2 (ANKRD2) is expressed in skeletal muscle, where plays a role inmuscle development, differentiation and adaptation to stress. Human skeletal muscle consists of threemajor fiber types: type 1 (slow-twitch, oxidative), type 2A (fast-twitch, oxidative) and type 2X (fast-twitch,glycolytic). ANKRD2 is reported to be primarily expressed in type 1 myofibers. However, recent findingson human single myofibers and our study of chicken muscles have shown that this protein may also beexpressed in type 2A fibers. Hence, our objective was to examine whether ANKRD2 is present in humanfast, type 2A muscle fibers using immunohistochemistry.Methods: Samples of large leg musclessoleus, gastrocnemius, vastusintermedius and vastuslateralis wereobtained from human cadaveric tissue. Serial cryosections were independently stained with anti-ANKRD2and antibodies for different myosin heavy chain isoforms (6H1 for type 2X, BF35 for type 1 and 2A, antiMHCs for type 1 and anti-MHCf for type 2A and 2X fibers). Immunostained tissues were analyzed by fluorescent microscopy.Results: In addition to slow, type 1, ANKRD2 wasfound expressed in fast, type 2A myofibers, which bothhave oxidative metabolism. Further, we did not observe ANDRD2 expression in glycolytic, type 2Xmyiofibers. This pattern of ANKRD2 expression was consistent across all examined muscles.Conclusion: Our resultsimplicate that the regulatory mechanism of ANKRD2 expression in human skeletal muscle is associated with oxidative metabolism, rather than muscle contraction speed.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - Determination of muscle fiber types expressing ANKRD2
EP  - 155
SP  - 155
UR  - https://hdl.handle.net/21.15107/rcub_intor_806
ER  - 
@conference{
author = "Novković, Mirjana and Vasić, Marko and Jasnić, Jovana and Milošević, Emilija and Milovanović, Mina and Savić, Slobodan and Kojić, Snežana",
year = "2023",
abstract = "Introduction: Ankyrin Repeat Domain 2 (ANKRD2) is expressed in skeletal muscle, where plays a role inmuscle development, differentiation and adaptation to stress. Human skeletal muscle consists of threemajor fiber types: type 1 (slow-twitch, oxidative), type 2A (fast-twitch, oxidative) and type 2X (fast-twitch,glycolytic). ANKRD2 is reported to be primarily expressed in type 1 myofibers. However, recent findingson human single myofibers and our study of chicken muscles have shown that this protein may also beexpressed in type 2A fibers. Hence, our objective was to examine whether ANKRD2 is present in humanfast, type 2A muscle fibers using immunohistochemistry.Methods: Samples of large leg musclessoleus, gastrocnemius, vastusintermedius and vastuslateralis wereobtained from human cadaveric tissue. Serial cryosections were independently stained with anti-ANKRD2and antibodies for different myosin heavy chain isoforms (6H1 for type 2X, BF35 for type 1 and 2A, antiMHCs for type 1 and anti-MHCf for type 2A and 2X fibers). Immunostained tissues were analyzed by fluorescent microscopy.Results: In addition to slow, type 1, ANKRD2 wasfound expressed in fast, type 2A myofibers, which bothhave oxidative metabolism. Further, we did not observe ANDRD2 expression in glycolytic, type 2Xmyiofibers. This pattern of ANKRD2 expression was consistent across all examined muscles.Conclusion: Our resultsimplicate that the regulatory mechanism of ANKRD2 expression in human skeletal muscle is associated with oxidative metabolism, rather than muscle contraction speed.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "Determination of muscle fiber types expressing ANKRD2",
pages = "155-155",
url = "https://hdl.handle.net/21.15107/rcub_intor_806"
}
Novković, M., Vasić, M., Jasnić, J., Milošević, E., Milovanović, M., Savić, S.,& Kojić, S.. (2023). Determination of muscle fiber types expressing ANKRD2. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 155-155.
https://hdl.handle.net/21.15107/rcub_intor_806
Novković M, Vasić M, Jasnić J, Milošević E, Milovanović M, Savić S, Kojić S. Determination of muscle fiber types expressing ANKRD2. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:155-155.
https://hdl.handle.net/21.15107/rcub_intor_806 .
Novković, Mirjana, Vasić, Marko, Jasnić, Jovana, Milošević, Emilija, Milovanović, Mina, Savić, Slobodan, Kojić, Snežana, "Determination of muscle fiber types expressing ANKRD2" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):155-155,
https://hdl.handle.net/21.15107/rcub_intor_806 .

Phenomapping for classification of doxorubicin-induced cardiomyopathy in rats

Pajović, Vladislav; Kovacshazi, Csenger; Kosić, Marija; Vasić, Marko; Dukić, Ljiljana; Brenner, Gabor B.; Giricz, Zoltan; Bajić, Dragana; Ferdinandy, Peter; Japundžić-Žigon, Nina

(Academic Press Inc Elsevier Science, San Diego, 2021)

TY  - JOUR
AU  - Pajović, Vladislav
AU  - Kovacshazi, Csenger
AU  - Kosić, Marija
AU  - Vasić, Marko
AU  - Dukić, Ljiljana
AU  - Brenner, Gabor B.
AU  - Giricz, Zoltan
AU  - Bajić, Dragana
AU  - Ferdinandy, Peter
AU  - Japundžić-Žigon, Nina
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1447
UR  - http://intor.torlakinstitut.com/handle/123456789/807
AB  - Cardiomyopathy resistant to treatment is the most serious adverse effect of doxorubicin (dox). The mechanisms of dox-induced cardiomyopathy (DCM) have been extensively studied in dilated forms of DCM. However, efficient treatment did not emerge. The aim of the present work was to revisit the experimental model of DCM in rats, to define phenotype/s and associate them to the changes in cardiac transcriptome. Male Wistar rats equipped with radiotelemetry device, were randomized in DOX group (5 mg/0,5 mL/kg, IV dox; n = 18) and CONT group (0,5 mL/kg IV saline; n = 6). Echocardiography, autonomic spectral markers and baroreceptor reflex evaluation was performed prior to, and after treatment. Blood samples were collected at the end of experimentation. Cardiac, renal and hepatic tissues were analysed post-mortem by histology. Changes in expression of key cardiac genes affected by dox were assessed by RT-qPCR. Phenotypes were identified by clustering non-redundant features using four different algorithms averaged by evidence accumulation cluster technique. The results emphasize the existence of two major phenotypes of DCM with comparably high mortality rates: phenotype 1 characterized by, left ventricular (LV) dilatation, thinning of LV posterior wall, reduced LV ejection fraction (LVEF) and fractional shortening (LVFS), decreased HR variability (HRV), decreased baroreceptor effectiveness index (BEI) and increased NT-proBNP; and phenotype 2 with LV hypertrophy - increased LV mass, preserved LVEF, LVFS, no changes in HRV and BEI and moderate NT-proBNP increase. Both phenotypes exhibited a genetic shift to a new-born program.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Toxicology and Applied Pharmacology
T1  - Phenomapping for classification of doxorubicin-induced cardiomyopathy in rats
VL  - 423
DO  - 10.1016/j.taap.2021.115579
ER  - 
@article{
author = "Pajović, Vladislav and Kovacshazi, Csenger and Kosić, Marija and Vasić, Marko and Dukić, Ljiljana and Brenner, Gabor B. and Giricz, Zoltan and Bajić, Dragana and Ferdinandy, Peter and Japundžić-Žigon, Nina",
year = "2021",
abstract = "Cardiomyopathy resistant to treatment is the most serious adverse effect of doxorubicin (dox). The mechanisms of dox-induced cardiomyopathy (DCM) have been extensively studied in dilated forms of DCM. However, efficient treatment did not emerge. The aim of the present work was to revisit the experimental model of DCM in rats, to define phenotype/s and associate them to the changes in cardiac transcriptome. Male Wistar rats equipped with radiotelemetry device, were randomized in DOX group (5 mg/0,5 mL/kg, IV dox; n = 18) and CONT group (0,5 mL/kg IV saline; n = 6). Echocardiography, autonomic spectral markers and baroreceptor reflex evaluation was performed prior to, and after treatment. Blood samples were collected at the end of experimentation. Cardiac, renal and hepatic tissues were analysed post-mortem by histology. Changes in expression of key cardiac genes affected by dox were assessed by RT-qPCR. Phenotypes were identified by clustering non-redundant features using four different algorithms averaged by evidence accumulation cluster technique. The results emphasize the existence of two major phenotypes of DCM with comparably high mortality rates: phenotype 1 characterized by, left ventricular (LV) dilatation, thinning of LV posterior wall, reduced LV ejection fraction (LVEF) and fractional shortening (LVFS), decreased HR variability (HRV), decreased baroreceptor effectiveness index (BEI) and increased NT-proBNP; and phenotype 2 with LV hypertrophy - increased LV mass, preserved LVEF, LVFS, no changes in HRV and BEI and moderate NT-proBNP increase. Both phenotypes exhibited a genetic shift to a new-born program.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Toxicology and Applied Pharmacology",
title = "Phenomapping for classification of doxorubicin-induced cardiomyopathy in rats",
volume = "423",
doi = "10.1016/j.taap.2021.115579"
}
Pajović, V., Kovacshazi, C., Kosić, M., Vasić, M., Dukić, L., Brenner, G. B., Giricz, Z., Bajić, D., Ferdinandy, P.,& Japundžić-Žigon, N.. (2021). Phenomapping for classification of doxorubicin-induced cardiomyopathy in rats. in Toxicology and Applied Pharmacology
Academic Press Inc Elsevier Science, San Diego., 423.
https://doi.org/10.1016/j.taap.2021.115579
Pajović V, Kovacshazi C, Kosić M, Vasić M, Dukić L, Brenner GB, Giricz Z, Bajić D, Ferdinandy P, Japundžić-Žigon N. Phenomapping for classification of doxorubicin-induced cardiomyopathy in rats. in Toxicology and Applied Pharmacology. 2021;423.
doi:10.1016/j.taap.2021.115579 .
Pajović, Vladislav, Kovacshazi, Csenger, Kosić, Marija, Vasić, Marko, Dukić, Ljiljana, Brenner, Gabor B., Giricz, Zoltan, Bajić, Dragana, Ferdinandy, Peter, Japundžić-Žigon, Nina, "Phenomapping for classification of doxorubicin-induced cardiomyopathy in rats" in Toxicology and Applied Pharmacology, 423 (2021),
https://doi.org/10.1016/j.taap.2021.115579 . .
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Varijabilitet srčane frekvencije i ekspresija ß-adrenergičkih receptora u kardiomiopatiji izazvanoj doksorubicinom

Vasić, Marko S.

(Univerzitet u Beogradu, Medicinski fakultet, 2019)

TY  - THES
AU  - Vasić, Marko S.
PY  - 2019
UR  - https://nardus.mpn.gov.rs/handle/123456789/11639
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7016
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:20624/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=51736335
UR  - http://intor.torlakinstitut.com/handle/123456789/654
AB  - Antraciklinski antibiotik doksorubicin pokazao se u višedecenijskoj kliničkoj praksi kao efikasan lek u terapiji brojnih maligniteta. Međutim, njegovu primenu ozbiljno sprečava pojava organske, a posebno srčane toksičnosti. Doksorubicinska kardiomiopatija razvija se najranije 30 dana, a nekada i nakon više godina od terapije doksorubicinom, rezistentna je na postojeću terapiju i ima veliku stopu smrtnosti. Premda su mehanizmi doksorubicinske kardiomiopatije dobro izučeni, još uvek ne postoje efikasna prevencija ni terapija. Zato je primena doksorbicina u kliničkoj praksi prihvatljiva samo uz stalni monitoring rada srca. U kardiološkoj praksi, varijabilitet srčane frekvencije (HRV) i senzitivnost arterijskog baroreceptorskog refleksa (sBRS) koriste se u prognostičke svrhe kod hipertenzije i ishemijske bolesti srca. U ovom radu ispitivani su dijagnostički i prognostički značaj HRV i sBRS za rànō otkrivanje kardiomiopatije prouzrokovane doksorubicinom i upoređivanje sa standardnim metodama – ehokardiografijom i serumskim markerima oštećenja kardiomiocita – srčanim troponinima. S obzirom na to da je uloga β-adrenergičkih receptora (β-AR) u nastanku srčane slabosti dobro poznata, pratili smo i ekspresiju srčanih β1- i β2-AR kod pacova tretiranih doksorubicinom, i poredili sa promenama HRV. Eksperimenti su izvedeni na odraslim mužjacima pacova Wistar soja, kojima je u femoralnu arteriju plasiran polietilenski kateter za registrovanje hemodinamskih parametara i uzorkovanje krvi. Eksperimentalnoj (DOX, n = 50) grupi, aplikovan je doksorubicin u kumulativnoj dozi od 15 mg/kg. Kontrolnoj grupi (CONT, n = 18) aplikovan je fiziološki rastvor u istoj zapremini. Procenjivana je opšta toksičnost doksorubicina i praćeni su hemodinamski ehokardiografski paramentri: pre tretmana, 35. dana (DOX35) i 70. dana (DOX70) nakon aplikacije doksorubicina. HRV analiziran je upotrebom nekoliko metóda: spektralne analize (Hilbert-Huangova transformacija), Poenkareovih dijagrama, aproksimativne entropije i entropijeuzorka...
AB  - Anthracycline antibiotic doxorubicin, used in clinical practice for several decades, has been shown as effective antineoplastic drug. Unfortunately, its usage is hindered due to multiple organotoxicity and especially cardiac toxicity. Doxorubicin-induced cardiomyopathy may develop 30 days, or even several years after following treatment. It is resistant to treatment, and has very high mortality rate. Although the mechanisms of doxorubicin-induced cardiomyopathy are well studied, there are still no effective treatment and prevention. Hence, the usage of doxorubicin in clinical practice is acceptable merely under close monitoring of cardiac function. In cardiology practice, heart rate variability (HRV) and baroreflex sensitivity (sBRS) are used as prognostic markers in hypertension and ischemic heart disease. Herein, we evaluated and compared diagnostic and prognostic values of HRV and sBRS in doxorubicin-induced cardiomyopathy to standard echocardiographic and serum cardiac troponin T and I methods. In addition, considering the pathophysiological role of β-adrenergic receptors (β-AR) in heart failure, we scrutinised the expression of β1- and β2-AR in doxorubicin-induced cardiomyopathy and its association to HRV changes. Experiments were performed on adult male Wistar rats, replete with femoral arterial catheter for blood pressure recording and blood sampling. Doxorubicin (DOX, n = 50) or saline (CONT, n = 18) were applied to rats in cumulative dose of 15 mg/kg (i.p.). General toxicity, cardiovascular hemodynamics and echocardiography were assessed before treatment, 35 days and 70 days after treatment. HRV and blood pressure variability (BPV) were evaluated by several methods (Hilbert-Huang frequency analysis, Poincaré plots, approximate entropy and sample entropy). The sequence method was used to evaluate sBRS. Levels of cardiac troponin T and I were measured by ECLIA method. β1-AR and β2-AR gene expression was measured by RT-qPCR...
PB  - Univerzitet u Beogradu, Medicinski fakultet
T2  - Univerzitet u Beogradu
T1  - Varijabilitet srčane frekvencije i ekspresija ß-adrenergičkih receptora u kardiomiopatiji izazvanoj doksorubicinom
UR  - https://hdl.handle.net/21.15107/rcub_nardus_11639
ER  - 
@phdthesis{
author = "Vasić, Marko S.",
year = "2019",
abstract = "Antraciklinski antibiotik doksorubicin pokazao se u višedecenijskoj kliničkoj praksi kao efikasan lek u terapiji brojnih maligniteta. Međutim, njegovu primenu ozbiljno sprečava pojava organske, a posebno srčane toksičnosti. Doksorubicinska kardiomiopatija razvija se najranije 30 dana, a nekada i nakon više godina od terapije doksorubicinom, rezistentna je na postojeću terapiju i ima veliku stopu smrtnosti. Premda su mehanizmi doksorubicinske kardiomiopatije dobro izučeni, još uvek ne postoje efikasna prevencija ni terapija. Zato je primena doksorbicina u kliničkoj praksi prihvatljiva samo uz stalni monitoring rada srca. U kardiološkoj praksi, varijabilitet srčane frekvencije (HRV) i senzitivnost arterijskog baroreceptorskog refleksa (sBRS) koriste se u prognostičke svrhe kod hipertenzije i ishemijske bolesti srca. U ovom radu ispitivani su dijagnostički i prognostički značaj HRV i sBRS za rànō otkrivanje kardiomiopatije prouzrokovane doksorubicinom i upoređivanje sa standardnim metodama – ehokardiografijom i serumskim markerima oštećenja kardiomiocita – srčanim troponinima. S obzirom na to da je uloga β-adrenergičkih receptora (β-AR) u nastanku srčane slabosti dobro poznata, pratili smo i ekspresiju srčanih β1- i β2-AR kod pacova tretiranih doksorubicinom, i poredili sa promenama HRV. Eksperimenti su izvedeni na odraslim mužjacima pacova Wistar soja, kojima je u femoralnu arteriju plasiran polietilenski kateter za registrovanje hemodinamskih parametara i uzorkovanje krvi. Eksperimentalnoj (DOX, n = 50) grupi, aplikovan je doksorubicin u kumulativnoj dozi od 15 mg/kg. Kontrolnoj grupi (CONT, n = 18) aplikovan je fiziološki rastvor u istoj zapremini. Procenjivana je opšta toksičnost doksorubicina i praćeni su hemodinamski ehokardiografski paramentri: pre tretmana, 35. dana (DOX35) i 70. dana (DOX70) nakon aplikacije doksorubicina. HRV analiziran je upotrebom nekoliko metóda: spektralne analize (Hilbert-Huangova transformacija), Poenkareovih dijagrama, aproksimativne entropije i entropijeuzorka..., Anthracycline antibiotic doxorubicin, used in clinical practice for several decades, has been shown as effective antineoplastic drug. Unfortunately, its usage is hindered due to multiple organotoxicity and especially cardiac toxicity. Doxorubicin-induced cardiomyopathy may develop 30 days, or even several years after following treatment. It is resistant to treatment, and has very high mortality rate. Although the mechanisms of doxorubicin-induced cardiomyopathy are well studied, there are still no effective treatment and prevention. Hence, the usage of doxorubicin in clinical practice is acceptable merely under close monitoring of cardiac function. In cardiology practice, heart rate variability (HRV) and baroreflex sensitivity (sBRS) are used as prognostic markers in hypertension and ischemic heart disease. Herein, we evaluated and compared diagnostic and prognostic values of HRV and sBRS in doxorubicin-induced cardiomyopathy to standard echocardiographic and serum cardiac troponin T and I methods. In addition, considering the pathophysiological role of β-adrenergic receptors (β-AR) in heart failure, we scrutinised the expression of β1- and β2-AR in doxorubicin-induced cardiomyopathy and its association to HRV changes. Experiments were performed on adult male Wistar rats, replete with femoral arterial catheter for blood pressure recording and blood sampling. Doxorubicin (DOX, n = 50) or saline (CONT, n = 18) were applied to rats in cumulative dose of 15 mg/kg (i.p.). General toxicity, cardiovascular hemodynamics and echocardiography were assessed before treatment, 35 days and 70 days after treatment. HRV and blood pressure variability (BPV) were evaluated by several methods (Hilbert-Huang frequency analysis, Poincaré plots, approximate entropy and sample entropy). The sequence method was used to evaluate sBRS. Levels of cardiac troponin T and I were measured by ECLIA method. β1-AR and β2-AR gene expression was measured by RT-qPCR...",
publisher = "Univerzitet u Beogradu, Medicinski fakultet",
journal = "Univerzitet u Beogradu",
title = "Varijabilitet srčane frekvencije i ekspresija ß-adrenergičkih receptora u kardiomiopatiji izazvanoj doksorubicinom",
url = "https://hdl.handle.net/21.15107/rcub_nardus_11639"
}
Vasić, M. S.. (2019). Varijabilitet srčane frekvencije i ekspresija ß-adrenergičkih receptora u kardiomiopatiji izazvanoj doksorubicinom. in Univerzitet u Beogradu
Univerzitet u Beogradu, Medicinski fakultet..
https://hdl.handle.net/21.15107/rcub_nardus_11639
Vasić MS. Varijabilitet srčane frekvencije i ekspresija ß-adrenergičkih receptora u kardiomiopatiji izazvanoj doksorubicinom. in Univerzitet u Beogradu. 2019;.
https://hdl.handle.net/21.15107/rcub_nardus_11639 .
Vasić, Marko S., "Varijabilitet srčane frekvencije i ekspresija ß-adrenergičkih receptora u kardiomiopatiji izazvanoj doksorubicinom" in Univerzitet u Beogradu (2019),
https://hdl.handle.net/21.15107/rcub_nardus_11639 .